Cetuximab-resistant oral squamous cell carcinoma cells become sensitive in anchorage-independent culture conditions through the activation of the EGFR/AKT pathway.


:We have previously shown that growth of the oral squamous cell carcinoma cell line SAS, is resistant to cetuximab in monolayer culture conditions, even though epidermal growth factor receptor (EGFR) was phosphorylated, but the growth of SAS aggregates was sensitive to cetuximab. In the present study, we demonstrate differences in the EGFR signaling pathways utilized by SAS cells in monolayer and suspension cultures at the molecular level. Cetuximab treatment of SAS cells in monolayer cultures inhibits the phosphorylation of EGFR and ERK, and reduces the cell migratory potency, but not cell proliferation. AG1478 treatment reduces the phosphorylation of EGFR, ERK and AKT, and affects cell growth in monolayer cultures. The phosphorylation levels of EGFR and AKT are significantly higher in SAS cell aggregates compared to monolayer cultures. Treatment with cetuximab and AG1478 reduces the growth of SAS aggregates and eliminates the phosphorylation of EGFR and AKT. Furthermore, proliferation of SAS aggregates is also inhibited by LY294002 and MK2206, which are inhibitors of PI3K and AKT, respectively. In addition, treatment with the lipid raft disruptor filipin III reduced the phosphorylation levels of EGFR and Akt in SAS aggregates, but not in SAS monolayer culture. These results suggest the possibility that ligands in the serum stimulate the phosphorylation of EGFR localized in lipid rafts leading to PI3K-AKT activation, which results in the growth of SAS aggregates, therefore resulting in the sensitivity of SAS aggregates to cetuximab.


Int J Oncol


Ohnishi Y,Yasui H,Kakudo K,Nozaki M




Has Abstract


2015-12-01 00:00:00












  • Differential modulation of cellular and viral promoters by p73 and p53.

    abstract::p73 has been shown to transcriptionally activate genes positively responsive to wild-type p53. In order to undertake a comparative study of functions of p53 and p73 we have cloned the cDNA of p73 from MCF-7 cells. Adenovirus onco-protein E1A inhibits the transactivation by p73; a deletion mutant of E1A incapable of in...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Deb D,Lanyi A,Scian M,Keiger J,Brown DR,Le Roith D,Deb SP,Deb S

    更新日期:2001-02-01 00:00:00

  • Localization of expression of fibroblast growth-factors and their receptors in pancreatic adenocarcinoma by in-situ hybridization.

    abstract::Growth factors may play a role in autocrine or paracrine growth control of tumour cells. We have now examined the expression pattern in vivo by in situ hybridization (ISH) on a series of 13 ductal adenocarcinomas of the pancreas using the non-radioactive digoxigenin system to generate specific antisense orientated rib...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Leung H,Hughes C,Kloppel G,Williamson R,Lemoine N

    更新日期:1994-06-01 00:00:00

  • Novel crosstalk between KLF4 and ZEB1 regulates gemcitabine resistance in pancreatic ductal adenocarcinoma.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with broad resistance to chemotherapeutic drugs. Krüppel-like factor 4 (KLF4) is a candidate tumor suppressor in PDAC. However, the precise role of KLF4 in gemcitabine resistance of PDAC remains largely unclear. In this study, we demonstrat...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Wang Z,Chen Y,Lin Y,Wang X,Cui X,Zhang Z,Xian G,Qin C

    更新日期:2017-10-01 00:00:00

  • A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors.

    abstract::Because K-Ras mutation and cyclooxygenase-2 (COX-2) overexpression are hallmarks of majority of pancreatic cancer patients, an approach to inhibit the progression and growth of pancreatic cancer using the simultaneous administration of agents that inhibit the function of both targets, should be considered. In the pres...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Ding N,Cui XX,Gao Z,Huang H,Wei X,Du Z,Lin Y,Shih WJ,Rabson AB,Conney AH,Hu C,Zheng X

    更新日期:2014-06-01 00:00:00

  • Nuclear morphometry for predicting cervical metastatic potential in laryngeal squamous-cell carcinoma.

    abstract::Quantitative nuclear morphometry (QNM) provides a reliable, reproducible method for measuring the degree of nuclear pleomorphism, a qualitative parameter widely incorporated into histopathological grading schemes. Nuclear shape has successfully been shown to predict primary prostate adenocarcinoma metastatic potential...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Donat T,Sakr W,Pienta K

    更新日期:1995-09-01 00:00:00

  • Comparative analysis of HPLC profile of cytosolic thymidine kinase activity between hepatoma and regenerating liver in rat with reference to phosphorylation.

    abstract::Thymidine kinase (TK) activity in rat hepatoma JB1 and AH136B was mainly due to cytosolic TK and was much higher than that in rat regenerating liver. Two forms of cytosolic TK, designated as TK-I and TK-II, were revealed in addition to mitochondrial TK in anion-exchange high performance liquid chromatography (HPLC) of...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Lin L,Islam MM,Du M,Ohmura Y,Hiwasa T,Fujimura S

    更新日期:1999-08-01 00:00:00

  • Heregulin-triggered Her-2/neu signaling enhances nuclear accumulation of p21WAF1/CIP1 and protects breast cancer cells from cisplatin-induced genotoxic damage.

    abstract::Elevated levels of p21WAF1/CIP1, an important mediator of DNA repair, have been observed in various aggressive tumors as well as linked to chemoresistance. We examined whether heregulin (HRG), a member of the EGF-like growth factor family closely related to breast cancer tumorigenesis and metastasis, modulates p21WAF1...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Menendez JA,Mehmi I,Lupu R

    更新日期:2005-03-01 00:00:00

  • Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer.

    abstract::PTEN, a gene encoding a dual specificity phosphatase, is frequently altered in endometrial carcinoma. Moreover, these alterations are observed even in atypical hyperplasia of the endometrium. This evidence suggests that mutation of PTEN is an early genetic alteration involved in endometrial carcinogenesis. Adenovirus-...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Sakurada A,Hamada H,Fukushige S,Yokoyama T,Yoshinaga K,Furukawa T,Sato S,Yajima A,Sato M,Fujimura S,Horii A

    更新日期:1999-12-01 00:00:00

  • Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer.

    abstract::ETS variant 1 (ETV1) is an oncogenic transcription factor. However, its role in colorectal cancer has remained understudied. The present study demonstrated that ETV1 downregulation led to reduced HCT116 colorectal cancer cell growth and clonogenic activity. Furthermore, the ETV1 mRNA levels were enhanced in colorectal...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Oh S,Song H,Freeman WM,Shin S,Janknecht R

    更新日期:2020-12-01 00:00:00

  • Downregulation of β3 integrin by miR-30a-5p modulates cell adhesion and invasion by interrupting Erk/Ets‑1 network in triple-negative breast cancer.

    abstract::Integrins are adhesion receptors involved in bidirectional signaling and are crucial for various cellular responses during normal homeostasis and pathological conditions, such as cancer progression and metastasis. In the present study, we demonstrated that blockage of β3 integrin-mediated cell- extracellular matrix in...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Li W,Liu C,Zhao C,Zhai L,Lv S

    更新日期:2016-03-01 00:00:00

  • Cell kinetic patterns in early gastric cancer.

    abstract::Early gastric cancers (EGC) may be subdivided into 2 groups by means of the use of mitotic index, apoptotic index and cell density: EGCs with high cell turnover and low cell density, which show high cell dissociation and, more frequently, lymph node invasion; EGCs with low cell turnover and high cell density. The same...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Spina D,Miracco C,Vindigni C,Gallorini M,Presenti L,Marrelli D,Roviello F,Pinto E,Filipe MI,Tosi P

    更新日期:1998-04-01 00:00:00

  • The dual inhibitory effect of thiostrepton on FoxM1 and EWS/FLI1 provides a novel therapeutic option for Ewing's sarcoma.

    abstract::The poor prognosis of Ewing's sarcoma (EWS), together with its high lethal recurrence rate and the side‑effects of current treatments, call for novel targeted therapies with greater curative effectiveness and substantially reduced side‑effects. The oncogenic chimeric protein EWS/FLI1 is the key malignancy driver in mo...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Sengupta A,Rahman M,Mateo-Lozano S,Tirado OM,Notario V

    更新日期:2013-09-01 00:00:00

  • Tumor hypoxia: Impact on gene amplification in glioblastoma.

    abstract::Gene amplification is frequently found in human glioblastoma but the mechanisms driving amplifications remain to be elucidated. Hypoxia as hallmark of glioblastoma is known to be involved in the induction of fragile sites that are central to gene amplification. We analyzed the potential of hypoxia (pO2 0%) and mini hy...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Fischer U,Radermacher J,Mayer J,Mehraein Y,Meese E

    更新日期:2008-09-01 00:00:00

  • Host cell reactivation of cisplatin-treated adenovirus is reduced in nucleotide excision repair deficient mammalian cells and several human tumour cells.

    abstract::Cisplatin is widely used for chemotherapy of a variety of human cancers. Cisplatin exerts its toxic effect by covalently binding to DNA, resulting in monofunctional adducts, intrastrand crosslinks, and interstrand crosslinks. Several recent reports suggest that the cellular capacity for DNA repair, especially nucleoti...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Bulmer J,Davis K,Rainbow A

    更新日期:1996-12-01 00:00:00

  • Establishment and characterization of GCSR1, a multi-drug resistant signet ring cell gastric cancer cell line.

    abstract::Signet ring cell gastric cancer (SRCGC) has very poor prognosis worldwide, and studying its molecular characteristics is urgent for improving the outcome. However, few well-characterized SRCGC cell lines are available for research. Therefore, we established a novel cell line GCSR1, from a Chinese male SRCGC patient. C...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Xu X,Qian LJ,Su XY,He KF,Jin KT,Gu LH,Feng JG,Li GL,Zhou Q,Xu ZZ,Wang HH,Zhang J,Cao J,Teng LS

    更新日期:2015-01-01 00:00:00

  • Sorafenib and TRAIL have synergistic effect on hepatocellular carcinoma.

    abstract::A multi-kinase inhibitor, sorafenib, was recently approved and is currently recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, HCC treatment outcomes are still poor and necessitate improvement. Therefore, we investigated the influence of sorafenib in ...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Nojiri K,Sugimoto K,Shiraki K,Tameda M,Inagaki Y,Ogura S,Kasai C,Kusagawa S,Yoneda M,Yamamoto N,Takei Y,Nobori T,Ito M

    更新日期:2013-01-01 00:00:00

  • Early responses of SiHa human squamous carcinoma cells to hypoxic signals.

    abstract::We compared the responses of c-Jun/AP-1 transcriptional complexes with those of NF-kappa B, an established hypoxia-inducible transcriptional complex, in hypoxic SiHa human squamous carcinoma cells. We observed that NF-kappa B was activated rapidly, while AP-1 activation was detectable only after prolonged hypoxia. How...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Laderoute K,Calaoagan J,Mendonca H,Ausserer W,Chen E,Giaccia A,Sutherland R

    更新日期:1996-05-01 00:00:00

  • Oncogenic mutation of the p53 gene derived from head and neck cancer prevents cells from undergoing apoptosis after DNA damage.

    abstract::A p53 functional analysis system, which can identify the types of abnormality of p53, such as loss of function, dominant negative function, or gain of oncogenic function, is now required. In this study, we examined the functional diversity of several mutations of p53 derived from human head and neck cancer cells. The ...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Kawamata H,Omotehara F,Nakashiro K,Uchida D,Shinagawa Y,Tachibana M,Imai Y,Fujimori T

    更新日期:2007-05-01 00:00:00

  • Autonomously replicating sequences identified in transcriptional regulatory regions of human N-myc gene.

    abstract::The regions upstream from the human N-myc gene were examined for both transcription and replication. The plasmids containing several N-myc regions linked to the bacterial chloramphenicol acetyltransferase (CAT) gene were transfected to human neuroblastoma IMR32 cells. The results indicated that the region spanning fro...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Nakagawa T,Imamura Y,Iguchiariga S,Ariga H

    更新日期:1994-09-01 00:00:00

  • Prognostic significance of cyclin expression in human osteosarcoma.

    abstract::To evaluate the distribution of cyclin protein expression, in relation to cell proliferation rate and clinical behavior, an immunohistochemical study was performed on 92 tumor samples of patients with high grade osteosarcoma (OS). A large cyclin A- and cyclin E-positive fraction was found respectively in 59% and 47% o...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Molendini L,Benassi MS,Magagnoli G,Merli M,Sollazzo MR,Ragazzini P,Gamberi G,Ferrari C,Balladelli A,Bacchini P,Picci P

    更新日期:1998-05-01 00:00:00

  • Concurrent use of multiple low dose chemotherapy agents with differing mechanisms of action as a strategy vs passive resistance: A pilot study.

    abstract::Resistance may be classified as active (or competitive) (due to excess amount of a factor) vs passive (or non-competitive) (due to a deficiency of a factor). Passive resistance may be important in human solid tumors. In passive resistance, the dose-response curve may be shallow, or may flatten at a relatively low dose...

    journal_title:International journal of oncology

    pub_type: 临床试验,杂志文章


    authors: Stewart DJ,Goel R,Gertler SZ,Huan S,Tomiak EM,Yau J,Cripps C,Evans WK

    更新日期:1999-10-01 00:00:00

  • Identification of TOMM34, which shows elevated expression in the majority of human colon cancers, as a novel drug target.

    abstract::In an attempt to isolate potential molecular targets for diagnosis, treatment and/or prevention of colorectal cancer (CRC), we have been analyzing expression profiles of clinical samples from CRC patients using genome-wide cDNA microarray. Among the genes up-regulated frequently in colorectal tumors, we here focused o...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Shimokawa T,Matsushima S,Tsunoda T,Tahara H,Nakamura Y,Furukawa Y

    更新日期:2006-08-01 00:00:00

  • Up-regulation of Frizzled-7 (FZD7) in human gastric cancer.

    abstract::Human Frizzled-7 (FZD7) and human FzE3, showing 98.8% nucleotide identity, encode almost identical WNT receptors with nine amino-acid substitutions. FzE3 is claimed to be expressed specifically in esophageal cancer. We determined the structure of the FZD7 gene and the FZD7 cDNA expressed in esophageal cancer. The FZD7...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Kirikoshi H,Sekihara H,Katoh M

    更新日期:2001-07-01 00:00:00

  • Interleukin-1 receptor antagonist (IL1RN) is associated with suppression of early carcinogenic events in human oral malignancies.

    abstract::Inflammatory abnormalities have been implicated in the pathogenesis of various human diseases, including cancer. Interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory molecule that modulates the biological activity of the proinflammatory cytokine, interleukin-1. The aim of this study was to examine t...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Shiiba M,Saito K,Yamagami H,Nakashima D,Higo M,Kasamatsu A,Sakamoto Y,Ogawara K,Uzawa K,Takiguchi Y,Tanzawa H

    更新日期:2015-05-01 00:00:00

  • Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2.

    abstract::Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared ...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Shang D,Wu J,Guo L,Xu Y,Liu L,Lu J

    更新日期:2017-05-01 00:00:00

  • DNA damage detected with gammaH2AX in endometrioid adenocarcinoma cell lines.

    abstract::Phosphorylation of histone H2AX (gammaH2AX) is a sensitive marker of DNA damage, particularly induction of DNA double-strand breaks. Using multiparameter cytometry we explored the effects of doxorubicin (DOX), cisplatin (CDDP) and 5-fluorouracil (5-FU) on four types of endometrioid adenocarcinoma cell lines (HEC-1A, H...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Ikeda M,Kurose A,Takatori E,Sugiyama T,Traganos F,Darzynkiewicz Z,Sawai T

    更新日期:2010-05-01 00:00:00

  • Tetramethypyrazine inhibits renal cell carcinoma cells through inhibition of NKG2D signaling pathways.

    abstract::Tetramethypyrazine (TMP), one of the active compounds extracted from the traditional Chinese medicinal herb (Chuanxiong), has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms have not been fully elucidated. In the present study, the anticancer ...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Luan Y,Liu J,Liu X,Xue X,Kong F,Sun C,Wang J,Liu L,Jia H

    更新日期:2016-10-01 00:00:00

  • Expression of mRNA for luteinizing hormone-releasing hormone receptors and epidermal growth factor receptors in human cancer cell lines.

    abstract::Conventional chemotherapy produces varying degrees of response in patients with many advanced cancers and has significant side effects. Receptors for luteinizing hormone-releasing hormone (LH-RH) are present in a high percentage of human ovarian, prostatic, breast and endometrial tumors and targeted chemotherapy based...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Lamharzi N,Halmos G,Armatis P,Schally AV

    更新日期:1998-03-01 00:00:00

  • Bomirski melanomas - a versatile and powerful model for pigment cell and melanoma research (review).

    abstract::Models of animal melanoma are still indispensable tools in oncological research because they can be studied in syngeneic hosts while human melanomas cannot. One such model is a family of melanomas which originated in 1959 from a spontaneous melanotic melanoma of the skin in Syrian hamster, the Bomirski melanomas. Curr...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Slominski A,Paus R

    更新日期:1993-02-01 00:00:00

  • Anticancer potential of novel curcumin analogs towards castrate-resistant prostate cancer.

    abstract::Prostate cancer is initially sensitive to hormone therapy; however, over time the majority of patients progress to a hormone-insensitive form classified as castration-resistant prostate cancer (CRPC). CRPC is highly metastatic and patients have a poor prognosis. Thus, new drugs for the treatment of this disease are re...

    journal_title:International journal of oncology

    pub_type: 杂志文章


    authors: Chen S,Nimick M,Cridge AG,Hawkins BC,Rosengren RJ

    更新日期:2018-02-01 00:00:00